The chromatographic separation using a conventional simulated moving bed separation apparatus comprises connecting a plurality of filler-packed columns in series endlessly end to end so as to form a fluid circulation passage (or called fluid flow circuit) composed of filler beds, in which a liquid is circulated in one direction; introducing a stock solution, which is a mixture containing a component to be separated, and an eluent and, wherein a liquid containing the component to be separated and a liquid containing other components is discharged.
The filler beds in said simulated moving bed separation apparatus have an eluent inlet, and an outlet for discharging a liquid containing strongly adsorbable (this liquid is called "extract" and is rich in the strongly adsorbable substances), a stock solution inlet, and an outlet for discharging a liquid containing weakly-adsorbable substances (this liquid is called "raffinate" and is rich in weakly adsorbable substances) in the direction of fluid flow and in this order. These inlets and outlets are intermittently and successively shifted in the direction of fluid flow maintaining the relative positional relation in the fluid circulation passage.
Such a commercial scale simulated moving bed separation apparatus is based on a system developed by Universal Oil Products Company (UOP) in 1967 and today various improved simulated moving bed separation apparatuses are being developed by many engineering companies. A typical example is a chemical plant where the separation of fructose, glucose, etc. is carried out.
Generally, operation of such a system is controlled by accurately measuring flow rate at each pump incorporated in the fluid circulation passage of a simulated moving bed separation apparatus or at each zone formed in the fluid circulation passage, analyzing the measured data with a computer, providing the operator with the thus obtained flow rate control data and manually controlling the operation.
Also an apparatus having a system, which monitors by means of a concentration meter with low pressure resistance (usually withstanding a pressure of not higher than 10 kg/cm.sup.2) provided in the fluid circulation passage, is known. In these proposed commercial scale simulated moving bed separation apparatuses, however, pressure resistance is generally set at not higher than 50 kg/cm.sup.2 since ion exchange resins, synthesized adsorbents, inorganic adsorbents (zeolite, for instance), etc. whose particle diameter is not less than 200 .mu.m are used. In simulated moving bed separation apparatuses using fillers for the HPLC level (1-100 .mu.m in diameter), generally the system pressure of the employed monitoring system is higher than 50 kg/cm.sup.2) In the simulated moving bed separation apparatus of this type, it is known that the employment of a shorter cycle type to increase the flow rate improves productivity.
In the current monitoring system and method of system control, it is desired to severely control the flow rate of the liquid circulating through the circulation passage. Further in the simulated moving bed separation apparatus using fillers of the type for HPLC, control of temperature and flow rate of the whole system must be more severely carried out than in the above-described low pressure system.
In simulated moving bed separation apparatuses using fillers of the type for HPLC, however, one cannot help determining the optimum operation conditions depending upon experience and intuition in order to produce products with consistent quality efficiently.
As an example of the monitoring method for chromatographic separation using a conventional low pressure simulated moving bed separation apparatus, it is known to measure the concentration of the solute discharged from the outlet every time the extract outlet of the raffinate outlet shifts intermittently with a constant time interval.
However, the concentration of the liquid discharged from the outlets is remarkably different between before and after the intermittent shifting of said outlets and, therefore, it is difficult to precisely monitor the concentration change. Also in the separation of optical isomers for instance, it is impossible to precisely grasp the separation state by mere monitoring of the concentration.
Japanese Laid-Open Patent Publication No. Hei 4-131104 discloses in "in a simulated moving bed chromatographic separation method, the method of controlling simulated moving bed separation process to adjust and maintain a predetermined component purity characterized by shortening or lengthening the interval with which the inlets and outlets are intermittently shifted by measuring the concentration of the fluid component at one or both of the inlet and outlet"
In the control method described in this patent publication, although the concentration is measured at the inlet a or outlet, time lag occurs because of the long distance between the outlet and the concentration detector making it impossible to obtain an accurate concentration determination. In addition to the time lag there is also diffusion and convection of the components in the extract and raffinate, and, therefore, an accurate concentration determination is impossible in this respect.
As described above, it was impossible to precisely determine the change in concentration or optical purity over time and to promptly judge the state of separation in the conventional simulated moving bed separation apparatus. As the state of separation cannot be judged instantly, it was impossible to set optimum operation conditions such as the time interval with which the inlet and outlet are intermittently shifted, flow rate and temperature of the circulating fluid, etc. and thus an efficient chromatographic separation was impossible.
An object of this invention is to provide a simulated moving bed separation apparatus which is able to accurately monitor concentration in each zone of the simulated moving beds. An object of this invention is to provide a simulated moving bed separation apparatus which can be operated with the same degree of simplicity as operating a liquid chromatographic apparatus. An object of the invention is to provide a simulated moving bed separation apparatus which can separate components a with high recovery rate, good productivity with and few rejects and little sample loss. Another object of this invention is to provide a simulated moving bed separation apparatus which can be easily and precisely operated without experience and intuition in operation of the apparatus.
An object of the invention is to provide a simulated moving bed separation apparatus with an incorporated automatic control system which enables real time monitoring of concentration pattern (purity pattern) in each zone, easy determination of the state of the operation and a long stable operation to produce a product of consistent quality.
Another object of the invention is to provide a simulated moving bed separation apparatus which achieves the technical effect of this invention.